A novel biparatopic hybrid antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy
oleh: Xiaoniu Miao, Yi Luo, Xi Huang, Suki M. Y. Lee, Zhijun Yuan, Yongzhou Tang, Liandi Chen, Chao Wang, Fan Wu, Yifeng Xu, Wenchao Jiang, Wei Gao, Xuedong Song, Yao Yan, Tuling Pang, Cheng Chen, Yuefeng Zou, Weihui Fu, Liping Wan, Javier Gilbert-Jaramillo, Michael Knight, Tiong Kit Tan, Pramila Rijal, Alain Townsend, Joanne Sun, Xiaolin Liu, William James, Andy Tsun, Yingda Xu
| Format: | Article |
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| Diterbitkan: | Taylor & Francis Group 2020-01-01 |
Deskripsi
In the absence of a proven effective vaccine preventing infection by SARS-CoV-2, or a proven drug to treat COVID-19, the positive results of passive immune therapy using convalescent serum provide a strong lead. We have developed a new class of tetravalent, biparatopic therapy, 89C8-ACE2. It combines the specificity of a monoclonal antibody (89C8) that recognizes the relatively conserved N-terminal domain of the viral Spike (S) glycoprotein, and the ectodomain of ACE2, which binds to the receptor-binding domain of S. This molecule shows exceptional performance in vitro, inhibiting the interaction of recombinant S1 to ACE2 and transduction of ACE2-overexpressing cells by S-pseudotyped lentivirus with IC50s substantially below 100 pM, and with potency approximately 100-fold greater than ACE2-Fc itself. Moreover, 89C8-ACE2 was able to neutralize authentic viral infection in a standard 96-h co-incubation assay at low nanomolar concentrations, making this class of molecule a promising lead for therapeutic applications.